An essential feature of cancer is its ability to evade the immune system. Multiple mechanisms are used for this purpose, including the disruption of antigen presentation and suppression of the immune response. The latter mechanism involves the activation of T-cell inhibition by recruiting regulatory T cells that weaken this response. Recent progress in understanding the ability of cancer to evade the immune system has paved the way to develop strategies to reverse this process and reactivate the immune system. Particularly, immune checkpoint signaling between T cells and tumor cells has been targeted with a new class of drug, immune checkpoint inhibitors. Immunotherapy has been an established and effective treatment in bladder cancer since 1976 when Morales and colleagues demonstrated that intravesical treatments with bacillus Calmette-Guérin can treat carcinoma in situ and prevent nonmuscle invasive urothelial cancer recurrence.^1,2 This treatment elicits a cytotoxic response via antigenic presentation by bladder tumor cells.

Cytotoxic T-lymphocyte-associated protein (CTLA)-4, programmed death-1 (PD-1) and programmed death-ligand-1 (PD-L1) are molecules that downregulate the immune response and are targets of therapeutic antibodies that have demonstrated clinical efficacy across a wide range of malignancies. Five such agents—pembrolizumab, atezolizumab, nivolumab, avelumab and durvalumab—were recently approved by the US Food and Drug Administration (FDA) for clinical use in patients with advanced urothelial cancers.³ This class of agents also has been approved for several other malignancies, most notably in melanoma, non-small cell lung cancer, and renal cell carcinoma.³

Immune Biology

CTLA-4 is expressed on activated CD4 and CD8 T cells and competes with CD28 on T cells to interact with the costimulatory B7 proteins on antigen presenting cells. The CD28/B7 interaction promotes T-cell activation and effector functions, and the CTLA-4/B7 interaction inhibits them. In addition, PD-1 is a receptor expressed on CD4 and CD8 T cells, T regulatory (Treg) cells, B cells and natural killer (NK) cells that interacts with its ligand PD-L1 to suppress the immune response. Urothelial cancer possesses features that make it an adequate target for immunotherapeutic agents. Primarily, it is characterized by a high-mutation load, which lends itself to an increased expression of immunogenic antigens on tumor cells.⁴

Immunotherapy Treatments in Cisplatin-Ineligible Patients

Cisplatin-based chemotherapy is the first-line treatment and standard of care in unresectable or metastatic urothelial cancer. However, many patients are unable to receive cisplatin secondary to renal dysfunction, poor performance status, or other comorbidities. Alternative cytotoxic therapies in the first-line setting such as carboplatin-based regimens are associated with inferior outcomes and poor tolerability. There is, therefore, a need for effective and well-tolerated therapies in cisplatin-ineligible patients (Table).

In the phase 2 Keynote-052 trial, 370 cisplatin-ineligible patients were treated with the anti-PD-1 antibody pembrolizumab 200 mg every 3 weeks for up to 2 years.⁵At a median follow-up of 9.5 months, the objective response rate (+ORR) was 29% for the entire cohort, with a 7% complete response (CR) rate, and a 22% partial response (PR) rate.⁵ The median duration of response had not been reached at the time of analysis. Responses were seen regardless of PD-L1 expression, although high response rates were noted in patients whose tumors had PD-L1 expression > 10%. Pembrolizumab had an acceptable tolerability profile in this population. The most common grade 3 or 4 treatment-related adverse event (AE) was fatigue at 2%; 5% of patients discontinued therapy due to treatment related AEs, whereas 17% of patients had immune-mediated AEs.⁵

Similarly, in a single-arm phase 2 trial, atezolizumab, an anti-PD-L1 antibody, dosed at 1,200 mg every 3 weeks was used as first-line therapy in 119 patients with advanced urothelial cancer who were cisplatin ineligible. At a median follow-up of 17 months, the ORR was 23%, with a 9% CR rate. The median duration of response had not been reached. Median progression free survival (PFS) was 2.7 months, whereas overall survival (OS) was 16 months. Eight percent of patients had an AE leading to treatment discontinuation, and 17% had immune-mediated AEs.⁶ Both pembrolizumab and atezolizumab were granted FDA approval in 2017 for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based chemotherapy.³

Immunotherapy Treatments After Progression With Cisplatin

Cytotoxic chemotherapy in the second-line setting with disease progression following platinum-based treatment has shown dismal responses, with a median OS of about 6 to 7 months.⁷ Immunotherapy provides an effective and a much-needed option in this scenario.

Five antibodies targeting the PD-1/PD-L1 pathway, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab, have been granted FDA approval for patients who have progressed during or after platinum-based therapy (Table).³ In the phase 3 Keynote-045 trial, 542 patients were randomly assigned to receive either pembrolizumab 200 mg administered every 3 weeks or investigator’s choice chemotherapy (paclitaxel, docetaxel, or vinflunine).⁷ Median OS was 10.3 months in the pembrolizumab group and 7.4 months in the chemotherapy group (hazard ratio for death, 0.73; P = .002). Serious (grade 3 or above) treatment-related AEs were significantly less frequent with pembrolizumab (15% vs 49.4%).⁷ In a phase 2 trial, 270 patients were treated with nivolumab, a PD-1 inhibitor, at a dose of 3 mg/kg given every 2 weeks.⁸ The ORR was 19.6%, while the median OS for the entire cohort was 7 months. Responses were seen at all levels of PD-L1 expression, although in patients whose tumor expressed PD-L1 ≥1%, median OS was 11.3 months.⁸

It should be noted that in a large phase 3 trial comparing atezolizumab with chemotherapy in the second-line setting, ORR and OS were not statistically different between the 2 groups, although the duration of response was longer with atezolizumab.⁹ In early phase trials, avelumab and durvalumab, both PD-L1 inhibitors showed an ORR of about 17%, with higher ORR seen in patients with tumors positive for PD-L1 expression.^10,11 The AE profile of immune checkpoint inhibitors is relatively favorable in clinical trials. The American Society of Clinical Oncology and National Comprehensive Cancer Network have jointly published evidence-based guidelines for the management of their immune related AEs.¹²

Future Directions

Several challenges have emerged with immunotherapy treatments. One issue is the relatively low ORRs for immune checkpoint inhibitors, ranging from 13.4% to 24% depending on the trial. Therefore, there is a need to identify reliable biomarkers and selection criteria to predict their efficacy and improve patient selection. Although tumor PD-L1 expression has shown some usefulness in this setting, responses have been noted in patients whose tumors have low or no expression of PD-L1. This low predictive accuracy is caused by several factors, including PD-L1 intratumor expression heterogeneity, primary vs metastatic site PD-L1 expression heterogeneity, lack of consensus on which PD-L1 assays and which value cutoffs to use, and the differences seen in marker expression depending on the freshness of the tissue specimen.

Other predictive biomarkers with potential include tumor gene expression profiles/tumor mutational load, T-cell and B-cell signatures. The optimal imaging modality and timing of this imaging for response assessment also is uncertain. So-called tumor pseudo-progression seen on imaging after treatment with these agents as a result of the immune/inflammatory response to the tumor is now a well-recognized phenomenon, but it can be challenging to differentiate from true disease progression. Other challenges include deciding on which immune checkpoint inhibitor to use given a lack of head-to-head comparisons of these immunotherapeutic agents, finding the proper drug doses to maximize efficacy, as well as determining the optimal duration of treatment in patients with continued response to immunotherapy. Many oncologists continue these treatments for up to 2 years in the setting of a significant or complete response.

Conclusion

Immune checkpoint inhibitors have emerged as pivotal treatments for patients with advanced urothelial cancer who are unfit to receive cisplatin in the first-line setting or who experience disease progression after cisplatin-based chemotherapy. This field continues to expand at a rapid pace due to multiple ongoing clinical trials assessing these agents, whether alone, in combination with cytotoxic, targeted, radiation therapies, or with other immune checkpoint inhibitors, both in the advanced as well as the neoadjuvant/adjuvant settings.

An essential feature of cancer is its ability to evade the immune system. Multiple mechanisms are used for this purpose, including the disruption of antigen presentation and suppression of the immune response. The latter mechanism involves the activation of T-cell inhibition by recruiting regulatory T cells that weaken this response. Recent progress in understanding the ability of cancer to evade the immune system has paved the way to develop strategies to reverse this process and reactivate the immune system. Particularly, immune checkpoint signaling between T cells and tumor cells has been targeted with a new class of drug, immune checkpoint inhibitors. Immunotherapy has been an established and effective treatment in bladder cancer since 1976 when Morales and colleagues demonstrated that intravesical treatments with bacillus Calmette-Guérin can treat carcinoma in situ and prevent nonmuscle invasive urothelial cancer recurrence.^1,2 This treatment elicits a cytotoxic response via antigenic presentation by bladder tumor cells.

Cytotoxic T-lymphocyte-associated protein (CTLA)-4, programmed death-1 (PD-1) and programmed death-ligand-1 (PD-L1) are molecules that downregulate the immune response and are targets of therapeutic antibodies that have demonstrated clinical efficacy across a wide range of malignancies. Five such agents—pembrolizumab, atezolizumab, nivolumab, avelumab and durvalumab—were recently approved by the US Food and Drug Administration (FDA) for clinical use in patients with advanced urothelial cancers.³ This class of agents also has been approved for several other malignancies, most notably in melanoma, non-small cell lung cancer, and renal cell carcinoma.³

Immune Biology

CTLA-4 is expressed on activated CD4 and CD8 T cells and competes with CD28 on T cells to interact with the costimulatory B7 proteins on antigen presenting cells. The CD28/B7 interaction promotes T-cell activation and effector functions, and the CTLA-4/B7 interaction inhibits them. In addition, PD-1 is a receptor expressed on CD4 and CD8 T cells, T regulatory (Treg) cells, B cells and natural killer (NK) cells that interacts with its ligand PD-L1 to suppress the immune response. Urothelial cancer possesses features that make it an adequate target for immunotherapeutic agents. Primarily, it is characterized by a high-mutation load, which lends itself to an increased expression of immunogenic antigens on tumor cells.⁴

Immunotherapy Treatments in Cisplatin-Ineligible Patients

Cisplatin-based chemotherapy is the first-line treatment and standard of care in unresectable or metastatic urothelial cancer. However, many patients are unable to receive cisplatin secondary to renal dysfunction, poor performance status, or other comorbidities. Alternative cytotoxic therapies in the first-line setting such as carboplatin-based regimens are associated with inferior outcomes and poor tolerability. There is, therefore, a need for effective and well-tolerated therapies in cisplatin-ineligible patients (Table).

In the phase 2 Keynote-052 trial, 370 cisplatin-ineligible patients were treated with the anti-PD-1 antibody pembrolizumab 200 mg every 3 weeks for up to 2 years.⁵At a median follow-up of 9.5 months, the objective response rate (+ORR) was 29% for the entire cohort, with a 7% complete response (CR) rate, and a 22% partial response (PR) rate.⁵ The median duration of response had not been reached at the time of analysis. Responses were seen regardless of PD-L1 expression, although high response rates were noted in patients whose tumors had PD-L1 expression > 10%. Pembrolizumab had an acceptable tolerability profile in this population. The most common grade 3 or 4 treatment-related adverse event (AE) was fatigue at 2%; 5% of patients discontinued therapy due to treatment related AEs, whereas 17% of patients had immune-mediated AEs.⁵

Similarly, in a single-arm phase 2 trial, atezolizumab, an anti-PD-L1 antibody, dosed at 1,200 mg every 3 weeks was used as first-line therapy in 119 patients with advanced urothelial cancer who were cisplatin ineligible. At a median follow-up of 17 months, the ORR was 23%, with a 9% CR rate. The median duration of response had not been reached. Median progression free survival (PFS) was 2.7 months, whereas overall survival (OS) was 16 months. Eight percent of patients had an AE leading to treatment discontinuation, and 17% had immune-mediated AEs.⁶ Both pembrolizumab and atezolizumab were granted FDA approval in 2017 for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based chemotherapy.³

Immunotherapy Treatments After Progression With Cisplatin

Cytotoxic chemotherapy in the second-line setting with disease progression following platinum-based treatment has shown dismal responses, with a median OS of about 6 to 7 months.⁷ Immunotherapy provides an effective and a much-needed option in this scenario.

Five antibodies targeting the PD-1/PD-L1 pathway, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab, have been granted FDA approval for patients who have progressed during or after platinum-based therapy (Table).³ In the phase 3 Keynote-045 trial, 542 patients were randomly assigned to receive either pembrolizumab 200 mg administered every 3 weeks or investigator’s choice chemotherapy (paclitaxel, docetaxel, or vinflunine).⁷ Median OS was 10.3 months in the pembrolizumab group and 7.4 months in the chemotherapy group (hazard ratio for death, 0.73; P = .002). Serious (grade 3 or above) treatment-related AEs were significantly less frequent with pembrolizumab (15% vs 49.4%).⁷ In a phase 2 trial, 270 patients were treated with nivolumab, a PD-1 inhibitor, at a dose of 3 mg/kg given every 2 weeks.⁸ The ORR was 19.6%, while the median OS for the entire cohort was 7 months. Responses were seen at all levels of PD-L1 expression, although in patients whose tumor expressed PD-L1 ≥1%, median OS was 11.3 months.⁸

It should be noted that in a large phase 3 trial comparing atezolizumab with chemotherapy in the second-line setting, ORR and OS were not statistically different between the 2 groups, although the duration of response was longer with atezolizumab.⁹ In early phase trials, avelumab and durvalumab, both PD-L1 inhibitors showed an ORR of about 17%, with higher ORR seen in patients with tumors positive for PD-L1 expression.^10,11 The AE profile of immune checkpoint inhibitors is relatively favorable in clinical trials. The American Society of Clinical Oncology and National Comprehensive Cancer Network have jointly published evidence-based guidelines for the management of their immune related AEs.¹²

Future Directions

Several challenges have emerged with immunotherapy treatments. One issue is the relatively low ORRs for immune checkpoint inhibitors, ranging from 13.4% to 24% depending on the trial. Therefore, there is a need to identify reliable biomarkers and selection criteria to predict their efficacy and improve patient selection. Although tumor PD-L1 expression has shown some usefulness in this setting, responses have been noted in patients whose tumors have low or no expression of PD-L1. This low predictive accuracy is caused by several factors, including PD-L1 intratumor expression heterogeneity, primary vs metastatic site PD-L1 expression heterogeneity, lack of consensus on which PD-L1 assays and which value cutoffs to use, and the differences seen in marker expression depending on the freshness of the tissue specimen.

Other predictive biomarkers with potential include tumor gene expression profiles/tumor mutational load, T-cell and B-cell signatures. The optimal imaging modality and timing of this imaging for response assessment also is uncertain. So-called tumor pseudo-progression seen on imaging after treatment with these agents as a result of the immune/inflammatory response to the tumor is now a well-recognized phenomenon, but it can be challenging to differentiate from true disease progression. Other challenges include deciding on which immune checkpoint inhibitor to use given a lack of head-to-head comparisons of these immunotherapeutic agents, finding the proper drug doses to maximize efficacy, as well as determining the optimal duration of treatment in patients with continued response to immunotherapy. Many oncologists continue these treatments for up to 2 years in the setting of a significant or complete response.

Conclusion

Immune checkpoint inhibitors have emerged as pivotal treatments for patients with advanced urothelial cancer who are unfit to receive cisplatin in the first-line setting or who experience disease progression after cisplatin-based chemotherapy. This field continues to expand at a rapid pace due to multiple ongoing clinical trials assessing these agents, whether alone, in combination with cytotoxic, targeted, radiation therapies, or with other immune checkpoint inhibitors, both in the advanced as well as the neoadjuvant/adjuvant settings.

An essential feature of cancer is its ability to evade the immune system. Multiple mechanisms are used for this purpose, including the disruption of antigen presentation and suppression of the immune response. The latter mechanism involves the activation of T-cell inhibition by recruiting regulatory T cells that weaken this response. Recent progress in understanding the ability of cancer to evade the immune system has paved the way to develop strategies to reverse this process and reactivate the immune system. Particularly, immune checkpoint signaling between T cells and tumor cells has been targeted with a new class of drug, immune checkpoint inhibitors. Immunotherapy has been an established and effective treatment in bladder cancer since 1976 when Morales and colleagues demonstrated that intravesical treatments with bacillus Calmette-Guérin can treat carcinoma in situ and prevent nonmuscle invasive urothelial cancer recurrence.^1,2 This treatment elicits a cytotoxic response via antigenic presentation by bladder tumor cells.

Cytotoxic T-lymphocyte-associated protein (CTLA)-4, programmed death-1 (PD-1) and programmed death-ligand-1 (PD-L1) are molecules that downregulate the immune response and are targets of therapeutic antibodies that have demonstrated clinical efficacy across a wide range of malignancies. Five such agents—pembrolizumab, atezolizumab, nivolumab, avelumab and durvalumab—were recently approved by the US Food and Drug Administration (FDA) for clinical use in patients with advanced urothelial cancers.³ This class of agents also has been approved for several other malignancies, most notably in melanoma, non-small cell lung cancer, and renal cell carcinoma.³

Immune Biology

CTLA-4 is expressed on activated CD4 and CD8 T cells and competes with CD28 on T cells to interact with the costimulatory B7 proteins on antigen presenting cells. The CD28/B7 interaction promotes T-cell activation and effector functions, and the CTLA-4/B7 interaction inhibits them. In addition, PD-1 is a receptor expressed on CD4 and CD8 T cells, T regulatory (Treg) cells, B cells and natural killer (NK) cells that interacts with its ligand PD-L1 to suppress the immune response. Urothelial cancer possesses features that make it an adequate target for immunotherapeutic agents. Primarily, it is characterized by a high-mutation load, which lends itself to an increased expression of immunogenic antigens on tumor cells.⁴

Immunotherapy Treatments in Cisplatin-Ineligible Patients

Cisplatin-based chemotherapy is the first-line treatment and standard of care in unresectable or metastatic urothelial cancer. However, many patients are unable to receive cisplatin secondary to renal dysfunction, poor performance status, or other comorbidities. Alternative cytotoxic therapies in the first-line setting such as carboplatin-based regimens are associated with inferior outcomes and poor tolerability. There is, therefore, a need for effective and well-tolerated therapies in cisplatin-ineligible patients (Table).

In the phase 2 Keynote-052 trial, 370 cisplatin-ineligible patients were treated with the anti-PD-1 antibody pembrolizumab 200 mg every 3 weeks for up to 2 years.⁵At a median follow-up of 9.5 months, the objective response rate (+ORR) was 29% for the entire cohort, with a 7% complete response (CR) rate, and a 22% partial response (PR) rate.⁵ The median duration of response had not been reached at the time of analysis. Responses were seen regardless of PD-L1 expression, although high response rates were noted in patients whose tumors had PD-L1 expression > 10%. Pembrolizumab had an acceptable tolerability profile in this population. The most common grade 3 or 4 treatment-related adverse event (AE) was fatigue at 2%; 5% of patients discontinued therapy due to treatment related AEs, whereas 17% of patients had immune-mediated AEs.⁵

Similarly, in a single-arm phase 2 trial, atezolizumab, an anti-PD-L1 antibody, dosed at 1,200 mg every 3 weeks was used as first-line therapy in 119 patients with advanced urothelial cancer who were cisplatin ineligible. At a median follow-up of 17 months, the ORR was 23%, with a 9% CR rate. The median duration of response had not been reached. Median progression free survival (PFS) was 2.7 months, whereas overall survival (OS) was 16 months. Eight percent of patients had an AE leading to treatment discontinuation, and 17% had immune-mediated AEs.⁶ Both pembrolizumab and atezolizumab were granted FDA approval in 2017 for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based chemotherapy.³

Immunotherapy Treatments After Progression With Cisplatin

Cytotoxic chemotherapy in the second-line setting with disease progression following platinum-based treatment has shown dismal responses, with a median OS of about 6 to 7 months.⁷ Immunotherapy provides an effective and a much-needed option in this scenario.

Five antibodies targeting the PD-1/PD-L1 pathway, pembrolizumab, nivolumab, atezolizumab, avelumab and durvalumab, have been granted FDA approval for patients who have progressed during or after platinum-based therapy (Table).³ In the phase 3 Keynote-045 trial, 542 patients were randomly assigned to receive either pembrolizumab 200 mg administered every 3 weeks or investigator’s choice chemotherapy (paclitaxel, docetaxel, or vinflunine).⁷ Median OS was 10.3 months in the pembrolizumab group and 7.4 months in the chemotherapy group (hazard ratio for death, 0.73; P = .002). Serious (grade 3 or above) treatment-related AEs were significantly less frequent with pembrolizumab (15% vs 49.4%).⁷ In a phase 2 trial, 270 patients were treated with nivolumab, a PD-1 inhibitor, at a dose of 3 mg/kg given every 2 weeks.⁸ The ORR was 19.6%, while the median OS for the entire cohort was 7 months. Responses were seen at all levels of PD-L1 expression, although in patients whose tumor expressed PD-L1 ≥1%, median OS was 11.3 months.⁸

It should be noted that in a large phase 3 trial comparing atezolizumab with chemotherapy in the second-line setting, ORR and OS were not statistically different between the 2 groups, although the duration of response was longer with atezolizumab.⁹ In early phase trials, avelumab and durvalumab, both PD-L1 inhibitors showed an ORR of about 17%, with higher ORR seen in patients with tumors positive for PD-L1 expression.^10,11 The AE profile of immune checkpoint inhibitors is relatively favorable in clinical trials. The American Society of Clinical Oncology and National Comprehensive Cancer Network have jointly published evidence-based guidelines for the management of their immune related AEs.¹²

Future Directions

Several challenges have emerged with immunotherapy treatments. One issue is the relatively low ORRs for immune checkpoint inhibitors, ranging from 13.4% to 24% depending on the trial. Therefore, there is a need to identify reliable biomarkers and selection criteria to predict their efficacy and improve patient selection. Although tumor PD-L1 expression has shown some usefulness in this setting, responses have been noted in patients whose tumors have low or no expression of PD-L1. This low predictive accuracy is caused by several factors, including PD-L1 intratumor expression heterogeneity, primary vs metastatic site PD-L1 expression heterogeneity, lack of consensus on which PD-L1 assays and which value cutoffs to use, and the differences seen in marker expression depending on the freshness of the tissue specimen.

Other predictive biomarkers with potential include tumor gene expression profiles/tumor mutational load, T-cell and B-cell signatures. The optimal imaging modality and timing of this imaging for response assessment also is uncertain. So-called tumor pseudo-progression seen on imaging after treatment with these agents as a result of the immune/inflammatory response to the tumor is now a well-recognized phenomenon, but it can be challenging to differentiate from true disease progression. Other challenges include deciding on which immune checkpoint inhibitor to use given a lack of head-to-head comparisons of these immunotherapeutic agents, finding the proper drug doses to maximize efficacy, as well as determining the optimal duration of treatment in patients with continued response to immunotherapy. Many oncologists continue these treatments for up to 2 years in the setting of a significant or complete response.

Conclusion

Immune checkpoint inhibitors have emerged as pivotal treatments for patients with advanced urothelial cancer who are unfit to receive cisplatin in the first-line setting or who experience disease progression after cisplatin-based chemotherapy. This field continues to expand at a rapid pace due to multiple ongoing clinical trials assessing these agents, whether alone, in combination with cytotoxic, targeted, radiation therapies, or with other immune checkpoint inhibitors, both in the advanced as well as the neoadjuvant/adjuvant settings.

Infants with bacteremic urinary tract infections on short-term versus long-term parenteral antibiotics before oral antibiotics had similar outcomes, according to a study.

AndyL/iStock/Getty Images Plus

While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.

“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.

In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.

Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).

A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).

Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).

No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.

“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.

In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”

The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”

The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.

[email protected]

SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.

Infants with bacteremic urinary tract infections on short-term versus long-term parenteral antibiotics before oral antibiotics had similar outcomes, according to a study.

AndyL/iStock/Getty Images Plus

While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.

“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.

In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.

Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).

A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).

Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).

No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.

“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.

In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”

The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”

The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.

[email protected]

SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.

Infants with bacteremic urinary tract infections on short-term versus long-term parenteral antibiotics before oral antibiotics had similar outcomes, according to a study.

AndyL/iStock/Getty Images Plus

While previous studies have shown short-term parenteral antibiotic therapy to be safe and equally effective in uncomplicated urinary tract infections (UTIs), short-term therapy safety in bacteremic UTI had not been established, Sanyukta Desai, MD, of the University of Cincinnati and Cincinnati Children’s Hospital and associates wrote in Pediatrics.

“As a result, infants with bacteremic UTI often receive prolonged courses of parenteral antibiotics, which can lead to long hospitalizations and increased costs,” they said.

In a multicenter, retrospective cohort study, Dr. Desai and associates analyzed a group of 115 infants aged 60 days or younger who were admitted to a group of 11 participating EDs between July 1, 2011, and June 30, 2016, if they had a UTI caused by a bacterial pathogen. Half of the infants were administered parenteral antibiotics for 7 days or less before being switched to oral antibiotics, and the rest were given parenteral antibiotics for more than 7 days before switching to oral. Infants were more likely to receive long-term parenteral treatment if they were ill appearing and had growth of a non–Escherichia coli organism.

Six infants (two in the short-term group, four in the long-term group) had a recurrent UTI, each one diagnosed between 15 and 30 days after discharge; the adjusted risk difference between the two groups was 3% (95% confidence interval, –5.8 to 12.7). Two of the infants in the long-term group with a recurrent UTI had a different organism than during the index infection. When comparing only the infants with growth of the same pathogen that caused the index UTI, the adjusted risk difference between the two groups was 0.2% (95% CI, –7.8 to 8.3).

A total of 15 infants (6 in the short-term group, 9 in the long-term group) had 30-day all-cause reutilization, with no significant difference between groups (adjusted risk difference, 3%; 95% CI, –14.6 to 20.4).

Mean length of stay was significantly longer in the long-term treatment group, compared with the short-term group (11 days vs. 5 days; adjusted mean difference, 6 days; 95% CI, 4.0-8.8).

No infants experienced a serious adverse event such as ICU readmission, need for mechanical ventilation or vasopressor use, or signs of neurologic sequelae within 30 days of discharge from the index hospitalization, the investigators noted. Peripherally inserted central catheters were required in 13 infants; of these, 1 infant had to revisit an ED because of a related mechanical complication.

“Researchers in future prospective studies should seek to establish the bioavailability and optimal dosing of oral antibiotics in young infants and assess if there are particular subpopulations of infants with bacteremic UTI who may benefit from longer courses of parenteral antibiotic therapy,” Dr. Desai and associates concluded.

In a related editorial, Natalia V. Leva, MD, and Hillary L. Copp, MD, of the University of California, San Francisco, noted that the study represents a “critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy.”

The question that remains is how long a duration of parenteral antibiotic is necessary, Dr. Leva and Dr. Copp wrote. “Desai et al. used a relatively arbitrary cutoff of 7 days on the basis of the distribution of antibiotic course among their patient population; however, this is likely more a reflection of clinical practice than it is evidence based.” They concluded that this study provided evidence that a “short course of parenteral antibiotics in infants [aged 60 days or younger] with bacteremic UTI is safe and effective. Although the current study does not address total duration of antibiotics [parenteral and oral], it does shine a light on where we should focus future research endeavors.”

The study authors reported that they had no conflicts of interest. The study was supported in part by a National Center for Advancing Translational Sciences grant and an Agency for Healthcare Research and Quality grant. The editorialists had no relevant conflicts of interest and received no external funding.

[email protected]

SOURCEs: Desai S et al. Pediatrics. 2019 Aug 20. doi: 10.1542/peds.2018-3844; Leva et al. 2019 Aug 20. doi: 10.1542/peds.2019-1611.

A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

Alexander Raths/Fotolia

In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

Alexander Raths/Fotolia

In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

A single, simple question about a patient’s experience of falls in the previous year can help predict their risk of fractures, a study suggests.

Alexander Raths/Fotolia

In Osteoporosis International, researchers reported the outcomes of a cohort study using Manitoba clinical registry data from 24,943 men and women aged 40 years and older within the province who had undergone a fracture-probability assessment, and had data on self-reported falls for the previous year and fracture outcomes.

William D. Leslie, MD, of the University of Manitoba in Winnipeg, and coauthors wrote that a frequent criticism of the FRAX fracture risk assessment tool was the fact that it didn’t include falls or fall risk in predicting fractures.

“Recent evidence derived from carefully conducted research cohort studies in men found that falls increase fracture risk independent of FRAX probability,” they wrote. “However, data are inconsistent with a paucity of evidence demonstrating usefulness of self-reported fall data as collected in routine clinical practice.”

Over a mean observation time of 2.7 years, 3.5% of the study population sustained at least one major osteoporotic fracture, 0.8% experienced a hip fracture, and 4.9% experienced any incident fracture.

The analysis showed an increased risk of fracture with the increasing number of self-reported falls experienced in the previous year. The risk of major osteoporotic fracture was 49% higher among individuals who reported one fall, 74% in those who reported two falls and 2.6-fold higher for those who reported three or more falls in the previous year, compared with those who did not report any falls.

A similar pattern was seen for any incident fracture and hip fracture, with a 3.4-fold higher risk of hip fracture seen in those who reported three or more falls. The study also showed an increase in mortality risk with increasing number of falls.

“We documented that a simple question regarding self-reported falls in the previous year could be easily collected during routine clinical practice and that this information was strongly predictive of short-term fracture risk independent of multiple clinical risk factors including fracture probability using the FRAX tool with BMD [bone mineral density],” the authors wrote.

The analysis did not find an interaction with age or sex and the number of falls.

John A. Kanis, MD, reported grants from Amgen, Lily, and Radius Health. Three other coauthors reported nothing to declare for the context of this article, but reported research grants, speaking honoraria, consultancies from a variety of pharmaceutical companies and organizations. The remaining five coauthors declared no conflicts of interest.

SOURCE: Leslie WD et al. Osteoporos Int. 2019 Aug. 2. doi: 10.1007/s00198-019-05106-3.

The history of abuse and genocide has its precursors in antiquity. A brief sketch of this history will provide some insights into the impact of intergenerational trauma and a rationale for the crisis of missing and murdered Indigenous women and girls in the United States and Canada, or Turtle Island, as the Indigenous People call it.

Such a review also will provide a partial explanation of why the suicide rate among non-Hispanic Native American or Alaska Native women increased by 139%¹ during 1999-2017 – a time when more Indigenous women were gaining access to law and medical school, as well as positions of authority in their tribes.

Church-, state-sanctioned transgressions

The psychological impact of our past history haunts us today. Papal bulletins – decrees from the pope – gave permission to Christian explorers to take land, wealth, and slaves from any nonbeliever. This permission was labeled the Doctrine of Discovery. It was incorporated into U.S. law in 1823, and by the Supreme Court case, Johnson v. M’intosh. It also provided rationale for the Indian Removal Act, which was passed on May 28, 1830, and signed into law by U.S. President Andrew Jackson. As a result of that law, Indigenous People were forced onto reservations, often removed from their traditional and sacred homelands. Many died during forced relocation.²

From the time of “discovery” by settlers until well into the 19th century, the U.S. governmental intent was genocide. It was manifest by the outright murder of Indigenous People, displacement from land, and the disruption of families when children were taken, put into boarding schools, and were forbidden to speak their language. Indigenous medicine people were killed or jailed for practicing their traditional ceremonies. Indigenous nations had their laws, languages, and agricultural practices denied them. Even today, they must practice U.S. law, adapt colonizing forms of land ownership, and engage in the economic practices of the dominant culture. The economic system currently in place rewards rape of the land and creates a trickle-up economy that keeps rewarding the rich at the expense of the poor. The economic system even gives corporations legal status as individuals, and, in some cases, is allowed to supersede the rights of Indigenous nations.

Today, the federal government still can appropriate land for minerals, pipelines,³ and even put indigenous land and water sovereignty at risk of contamination and pollution by mines established upstream.⁴ Most of those practices are repugnant to Indigenous nations. The Doctrine of Discovery established prior to 1492 is still alive and well on Turtle Island.

It is this background that denies the rights of Mother Earth, and this backdrop that, in turn, generalizes the denial of the rights of Indigenous women. There are women today, who, against their will and knowledge, have been sterilized.⁵ There are cases in which women have been raped and beaten, and their perpetrators were never been brought to justice.⁶ There are jurisdictional issues in the federal law that keep non-native perpetrators from being punished for their actions on tribal sovereign land.

This history and those current practices affect Indigenous families. Historical trauma produces epigenetic changes⁷ that create more anxiety and depression. Families in which one or both parents were taken away have a harder time providing a loving, safe, addiction-free environment for their children. Children often have high scores on measurements of adverse childhood experiences and suffer PTSD. As psychiatrists, we have treated PTSD from residential and boarding school survivors, families with family members who were victims of being missing or murdered, and survivors of sexual abuse – both in the United States and Canada. According to the final Canadian report of the inquiry into missing and murdered Indigenous women and girls, the murder rate for Indigenous women was 12 times that of non-Indigenous women.8

We assert that this combination of historical trauma and current social factors contributes to depression, PTSD, and anxiety disorders that currently feed the rise in attempted and completed suicide. Less-than-optimal educational opportunities and unemployment, often above 10% on reservations,⁹ along with food insecurity, accentuate the settings in which women and girls live.

Women achieving despite challenges

Yet, Indigenous women are making great strides within their cultures and communities. For example, Indigenous women are leading language revitalization, and within their culture, are healers and carriers of knowledge. Many Indigenous women are doctors, lawyers, dentists, teachers, poets, authors, and artists^.10 Voters in last year’s midterms elected two Native American women to the U.S. Congress. Often, however, those achievements within the Western culture come at a cost, and some might have difficulty balancing those roles with their traditional cultures.

Current societal pressures feed the rise of suicide. Santa Fe, N.M., is known for its affluence and reputation as a tricultural city of Anglos, Hispanics, and Native Americans, and yet, a recent health impact assessment survey of urban Indigenous families stated that food insecurity was the leading concern for those families. Unemployment on the Navajo Nation is above 50%.¹¹ The Indian Health Service (IHS) in the United States, which provides the majority of mental services to the Indigenous population, has identified mental health issues as the No. 1 health problem. However, only 7% of the IHS budget is allocated for mental health and substance abuse services. This represents an underfudging of services to American Indian and Alaska Native communities. In fact, there were only two psychiatrists per 100,000 people served by the IHS, which is one-seventh the number of psychiatrists available to the general population in the United States.¹²

Best practices for psychiatrists working with Indigenous women demands that we know the history, know how that history is still being manifest in subtle ways, and understand how such antiquated papal bulletins as the Doctrine of Discovery still operate to justify the taking and misuse of indigenous land. We must realize that the dominant economic systems, laws, and policing strategies are imposed on cultures that are sophisticated in their own right. This will then allow compassionate care with a level of understanding.

It also is critical to avoid stereotypes and misdiagnoses, and clinicians should realize that much of what is seen is not personality disorder but aspects of trauma and PTSD. ¹³

We can advocate at all levels, considering that the role of the federal government, the state, corporations, tribes, families, and provision of quality care to individuals can continue the positive collective advancement of women, and reduce the morbidity and mortality associated with suicide attempts.

We need to be sensitive to our patients and their risks of suicide. Treat suicidal ideation as the serious threat that it is. Address the depression, anxiety, PTSD, historical trauma, substance abuse, emotional dysregulation, and loss of relationship in persons with attachment disorders as serious and valid life events than can lead to serious consequences – including completed suicide.

Indigenous women are resilient, and the approach should be to also balance knowledge of those potential barriers with validating the feminine, and supporting the traditional roles of women and men that value women and children, and revere the matriarchs. Encouraging and supporting Indigenous resurgence of cultural practices and values is significant for positive outcomes for healing and wellness. Doing so can carry a greater meaning within Indigenous and First Nations society.
 

References

1. Curtin SC and H Hedegaard. Suicide rates for females and males by race and ethnicity: United States, 1999 and 2017. NCHS Health E-Stat. 2019.

2. Anderson GC. Ethnic cleansing and the Indian: The crime that should haunt America. Norman, Okla.: University of Oklahoma Press, 2014.

3. Rausch N. “Standing Rock, Morton County work to mend relationships post-DAPL protests.” Billingsgazette.com. Aug 10, 2019.

4. Roy A. “5 ways the government keeps Native Americans in poverty.” Forbes.com. Mar 13, 2014.

5. Blakemore E. “The little-known history of forced sterilization of Native American women.” JSTOR.org. Aug 25, 2016.

6. Bleir G and A Zoledziowski. “Murdered and missing Native American women challenge police and courts.” Publicintegrity.org. Aug 27, 2018.

7. Brockie TN et al. A framework to examine the role of epigenetics in health disparities among Native Americans. Nurs Res Prac. 2013;2013:410395.

8. “Reclaiming power and place: The final report of the national inquiry into missing and murdered Indigenous women and girls.” Vancouver: Privy Office. Jun 3, 2019.

9. Hagan S. “Where U.S. unemployment is still sky-high: Indian reservations.” Bloomberg.com. Apr 5, 2018.

10. Morin B. “Meet 10 Indigenous women who are making the world a better place.” Indian Country Today. Jul 1, 2019.

11. Fact sheet. Discovernavajo.com.

12. Sarche M and P Spicer. Poverty and health disparities for American Indian and Alaska Native children: Current knowledge and future prospects. Ann NY Acad Sci. 2008 Jul 25;1136:126-36.

13. Lewis-Fernández R et al. Culture and psychiatric evaluation: Operationalizing cultural formulation for DSM-5. Psychiatry. 2014 Summer;77(2):130-54.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local Indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association.

Dr. Neidhardt is a board-certified psychiatrist who lives in Santa Fe and has an integrative, holistic psychiatric practice that also specializes in trauma-focused therapy. He has provided care for Indigenous People in the Southwest United States and in Canada, and has worked with Navajo medicine people to develop training for mental health professionals with his wife, Dr. Mary Hasbah Roessel. Dr. Reinhardt is a life fellow of the APA.

The history of abuse and genocide has its precursors in antiquity. A brief sketch of this history will provide some insights into the impact of intergenerational trauma and a rationale for the crisis of missing and murdered Indigenous women and girls in the United States and Canada, or Turtle Island, as the Indigenous People call it.

Such a review also will provide a partial explanation of why the suicide rate among non-Hispanic Native American or Alaska Native women increased by 139%¹ during 1999-2017 – a time when more Indigenous women were gaining access to law and medical school, as well as positions of authority in their tribes.

Church-, state-sanctioned transgressions

The psychological impact of our past history haunts us today. Papal bulletins – decrees from the pope – gave permission to Christian explorers to take land, wealth, and slaves from any nonbeliever. This permission was labeled the Doctrine of Discovery. It was incorporated into U.S. law in 1823, and by the Supreme Court case, Johnson v. M’intosh. It also provided rationale for the Indian Removal Act, which was passed on May 28, 1830, and signed into law by U.S. President Andrew Jackson. As a result of that law, Indigenous People were forced onto reservations, often removed from their traditional and sacred homelands. Many died during forced relocation.²

From the time of “discovery” by settlers until well into the 19th century, the U.S. governmental intent was genocide. It was manifest by the outright murder of Indigenous People, displacement from land, and the disruption of families when children were taken, put into boarding schools, and were forbidden to speak their language. Indigenous medicine people were killed or jailed for practicing their traditional ceremonies. Indigenous nations had their laws, languages, and agricultural practices denied them. Even today, they must practice U.S. law, adapt colonizing forms of land ownership, and engage in the economic practices of the dominant culture. The economic system currently in place rewards rape of the land and creates a trickle-up economy that keeps rewarding the rich at the expense of the poor. The economic system even gives corporations legal status as individuals, and, in some cases, is allowed to supersede the rights of Indigenous nations.

Today, the federal government still can appropriate land for minerals, pipelines,³ and even put indigenous land and water sovereignty at risk of contamination and pollution by mines established upstream.⁴ Most of those practices are repugnant to Indigenous nations. The Doctrine of Discovery established prior to 1492 is still alive and well on Turtle Island.

It is this background that denies the rights of Mother Earth, and this backdrop that, in turn, generalizes the denial of the rights of Indigenous women. There are women today, who, against their will and knowledge, have been sterilized.⁵ There are cases in which women have been raped and beaten, and their perpetrators were never been brought to justice.⁶ There are jurisdictional issues in the federal law that keep non-native perpetrators from being punished for their actions on tribal sovereign land.

This history and those current practices affect Indigenous families. Historical trauma produces epigenetic changes⁷ that create more anxiety and depression. Families in which one or both parents were taken away have a harder time providing a loving, safe, addiction-free environment for their children. Children often have high scores on measurements of adverse childhood experiences and suffer PTSD. As psychiatrists, we have treated PTSD from residential and boarding school survivors, families with family members who were victims of being missing or murdered, and survivors of sexual abuse – both in the United States and Canada. According to the final Canadian report of the inquiry into missing and murdered Indigenous women and girls, the murder rate for Indigenous women was 12 times that of non-Indigenous women.8

We assert that this combination of historical trauma and current social factors contributes to depression, PTSD, and anxiety disorders that currently feed the rise in attempted and completed suicide. Less-than-optimal educational opportunities and unemployment, often above 10% on reservations,⁹ along with food insecurity, accentuate the settings in which women and girls live.

Women achieving despite challenges

Yet, Indigenous women are making great strides within their cultures and communities. For example, Indigenous women are leading language revitalization, and within their culture, are healers and carriers of knowledge. Many Indigenous women are doctors, lawyers, dentists, teachers, poets, authors, and artists^.10 Voters in last year’s midterms elected two Native American women to the U.S. Congress. Often, however, those achievements within the Western culture come at a cost, and some might have difficulty balancing those roles with their traditional cultures.

Current societal pressures feed the rise of suicide. Santa Fe, N.M., is known for its affluence and reputation as a tricultural city of Anglos, Hispanics, and Native Americans, and yet, a recent health impact assessment survey of urban Indigenous families stated that food insecurity was the leading concern for those families. Unemployment on the Navajo Nation is above 50%.¹¹ The Indian Health Service (IHS) in the United States, which provides the majority of mental services to the Indigenous population, has identified mental health issues as the No. 1 health problem. However, only 7% of the IHS budget is allocated for mental health and substance abuse services. This represents an underfudging of services to American Indian and Alaska Native communities. In fact, there were only two psychiatrists per 100,000 people served by the IHS, which is one-seventh the number of psychiatrists available to the general population in the United States.¹²

Best practices for psychiatrists working with Indigenous women demands that we know the history, know how that history is still being manifest in subtle ways, and understand how such antiquated papal bulletins as the Doctrine of Discovery still operate to justify the taking and misuse of indigenous land. We must realize that the dominant economic systems, laws, and policing strategies are imposed on cultures that are sophisticated in their own right. This will then allow compassionate care with a level of understanding.

It also is critical to avoid stereotypes and misdiagnoses, and clinicians should realize that much of what is seen is not personality disorder but aspects of trauma and PTSD. ¹³

We can advocate at all levels, considering that the role of the federal government, the state, corporations, tribes, families, and provision of quality care to individuals can continue the positive collective advancement of women, and reduce the morbidity and mortality associated with suicide attempts.

We need to be sensitive to our patients and their risks of suicide. Treat suicidal ideation as the serious threat that it is. Address the depression, anxiety, PTSD, historical trauma, substance abuse, emotional dysregulation, and loss of relationship in persons with attachment disorders as serious and valid life events than can lead to serious consequences – including completed suicide.

Indigenous women are resilient, and the approach should be to also balance knowledge of those potential barriers with validating the feminine, and supporting the traditional roles of women and men that value women and children, and revere the matriarchs. Encouraging and supporting Indigenous resurgence of cultural practices and values is significant for positive outcomes for healing and wellness. Doing so can carry a greater meaning within Indigenous and First Nations society.
 

References

1. Curtin SC and H Hedegaard. Suicide rates for females and males by race and ethnicity: United States, 1999 and 2017. NCHS Health E-Stat. 2019.

2. Anderson GC. Ethnic cleansing and the Indian: The crime that should haunt America. Norman, Okla.: University of Oklahoma Press, 2014.

3. Rausch N. “Standing Rock, Morton County work to mend relationships post-DAPL protests.” Billingsgazette.com. Aug 10, 2019.

4. Roy A. “5 ways the government keeps Native Americans in poverty.” Forbes.com. Mar 13, 2014.

5. Blakemore E. “The little-known history of forced sterilization of Native American women.” JSTOR.org. Aug 25, 2016.

6. Bleir G and A Zoledziowski. “Murdered and missing Native American women challenge police and courts.” Publicintegrity.org. Aug 27, 2018.

7. Brockie TN et al. A framework to examine the role of epigenetics in health disparities among Native Americans. Nurs Res Prac. 2013;2013:410395.

8. “Reclaiming power and place: The final report of the national inquiry into missing and murdered Indigenous women and girls.” Vancouver: Privy Office. Jun 3, 2019.

9. Hagan S. “Where U.S. unemployment is still sky-high: Indian reservations.” Bloomberg.com. Apr 5, 2018.

10. Morin B. “Meet 10 Indigenous women who are making the world a better place.” Indian Country Today. Jul 1, 2019.

11. Fact sheet. Discovernavajo.com.

12. Sarche M and P Spicer. Poverty and health disparities for American Indian and Alaska Native children: Current knowledge and future prospects. Ann NY Acad Sci. 2008 Jul 25;1136:126-36.

13. Lewis-Fernández R et al. Culture and psychiatric evaluation: Operationalizing cultural formulation for DSM-5. Psychiatry. 2014 Summer;77(2):130-54.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local Indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association.

Dr. Neidhardt is a board-certified psychiatrist who lives in Santa Fe and has an integrative, holistic psychiatric practice that also specializes in trauma-focused therapy. He has provided care for Indigenous People in the Southwest United States and in Canada, and has worked with Navajo medicine people to develop training for mental health professionals with his wife, Dr. Mary Hasbah Roessel. Dr. Reinhardt is a life fellow of the APA.

The history of abuse and genocide has its precursors in antiquity. A brief sketch of this history will provide some insights into the impact of intergenerational trauma and a rationale for the crisis of missing and murdered Indigenous women and girls in the United States and Canada, or Turtle Island, as the Indigenous People call it.

Such a review also will provide a partial explanation of why the suicide rate among non-Hispanic Native American or Alaska Native women increased by 139%¹ during 1999-2017 – a time when more Indigenous women were gaining access to law and medical school, as well as positions of authority in their tribes.

Church-, state-sanctioned transgressions

The psychological impact of our past history haunts us today. Papal bulletins – decrees from the pope – gave permission to Christian explorers to take land, wealth, and slaves from any nonbeliever. This permission was labeled the Doctrine of Discovery. It was incorporated into U.S. law in 1823, and by the Supreme Court case, Johnson v. M’intosh. It also provided rationale for the Indian Removal Act, which was passed on May 28, 1830, and signed into law by U.S. President Andrew Jackson. As a result of that law, Indigenous People were forced onto reservations, often removed from their traditional and sacred homelands. Many died during forced relocation.²

From the time of “discovery” by settlers until well into the 19th century, the U.S. governmental intent was genocide. It was manifest by the outright murder of Indigenous People, displacement from land, and the disruption of families when children were taken, put into boarding schools, and were forbidden to speak their language. Indigenous medicine people were killed or jailed for practicing their traditional ceremonies. Indigenous nations had their laws, languages, and agricultural practices denied them. Even today, they must practice U.S. law, adapt colonizing forms of land ownership, and engage in the economic practices of the dominant culture. The economic system currently in place rewards rape of the land and creates a trickle-up economy that keeps rewarding the rich at the expense of the poor. The economic system even gives corporations legal status as individuals, and, in some cases, is allowed to supersede the rights of Indigenous nations.

Today, the federal government still can appropriate land for minerals, pipelines,³ and even put indigenous land and water sovereignty at risk of contamination and pollution by mines established upstream.⁴ Most of those practices are repugnant to Indigenous nations. The Doctrine of Discovery established prior to 1492 is still alive and well on Turtle Island.

It is this background that denies the rights of Mother Earth, and this backdrop that, in turn, generalizes the denial of the rights of Indigenous women. There are women today, who, against their will and knowledge, have been sterilized.⁵ There are cases in which women have been raped and beaten, and their perpetrators were never been brought to justice.⁶ There are jurisdictional issues in the federal law that keep non-native perpetrators from being punished for their actions on tribal sovereign land.

This history and those current practices affect Indigenous families. Historical trauma produces epigenetic changes⁷ that create more anxiety and depression. Families in which one or both parents were taken away have a harder time providing a loving, safe, addiction-free environment for their children. Children often have high scores on measurements of adverse childhood experiences and suffer PTSD. As psychiatrists, we have treated PTSD from residential and boarding school survivors, families with family members who were victims of being missing or murdered, and survivors of sexual abuse – both in the United States and Canada. According to the final Canadian report of the inquiry into missing and murdered Indigenous women and girls, the murder rate for Indigenous women was 12 times that of non-Indigenous women.8

We assert that this combination of historical trauma and current social factors contributes to depression, PTSD, and anxiety disorders that currently feed the rise in attempted and completed suicide. Less-than-optimal educational opportunities and unemployment, often above 10% on reservations,⁹ along with food insecurity, accentuate the settings in which women and girls live.

Women achieving despite challenges

Yet, Indigenous women are making great strides within their cultures and communities. For example, Indigenous women are leading language revitalization, and within their culture, are healers and carriers of knowledge. Many Indigenous women are doctors, lawyers, dentists, teachers, poets, authors, and artists^.10 Voters in last year’s midterms elected two Native American women to the U.S. Congress. Often, however, those achievements within the Western culture come at a cost, and some might have difficulty balancing those roles with their traditional cultures.

Current societal pressures feed the rise of suicide. Santa Fe, N.M., is known for its affluence and reputation as a tricultural city of Anglos, Hispanics, and Native Americans, and yet, a recent health impact assessment survey of urban Indigenous families stated that food insecurity was the leading concern for those families. Unemployment on the Navajo Nation is above 50%.¹¹ The Indian Health Service (IHS) in the United States, which provides the majority of mental services to the Indigenous population, has identified mental health issues as the No. 1 health problem. However, only 7% of the IHS budget is allocated for mental health and substance abuse services. This represents an underfudging of services to American Indian and Alaska Native communities. In fact, there were only two psychiatrists per 100,000 people served by the IHS, which is one-seventh the number of psychiatrists available to the general population in the United States.¹²

Best practices for psychiatrists working with Indigenous women demands that we know the history, know how that history is still being manifest in subtle ways, and understand how such antiquated papal bulletins as the Doctrine of Discovery still operate to justify the taking and misuse of indigenous land. We must realize that the dominant economic systems, laws, and policing strategies are imposed on cultures that are sophisticated in their own right. This will then allow compassionate care with a level of understanding.

It also is critical to avoid stereotypes and misdiagnoses, and clinicians should realize that much of what is seen is not personality disorder but aspects of trauma and PTSD. ¹³

We can advocate at all levels, considering that the role of the federal government, the state, corporations, tribes, families, and provision of quality care to individuals can continue the positive collective advancement of women, and reduce the morbidity and mortality associated with suicide attempts.

We need to be sensitive to our patients and their risks of suicide. Treat suicidal ideation as the serious threat that it is. Address the depression, anxiety, PTSD, historical trauma, substance abuse, emotional dysregulation, and loss of relationship in persons with attachment disorders as serious and valid life events than can lead to serious consequences – including completed suicide.

Indigenous women are resilient, and the approach should be to also balance knowledge of those potential barriers with validating the feminine, and supporting the traditional roles of women and men that value women and children, and revere the matriarchs. Encouraging and supporting Indigenous resurgence of cultural practices and values is significant for positive outcomes for healing and wellness. Doing so can carry a greater meaning within Indigenous and First Nations society.
 

References

1. Curtin SC and H Hedegaard. Suicide rates for females and males by race and ethnicity: United States, 1999 and 2017. NCHS Health E-Stat. 2019.

2. Anderson GC. Ethnic cleansing and the Indian: The crime that should haunt America. Norman, Okla.: University of Oklahoma Press, 2014.

3. Rausch N. “Standing Rock, Morton County work to mend relationships post-DAPL protests.” Billingsgazette.com. Aug 10, 2019.

4. Roy A. “5 ways the government keeps Native Americans in poverty.” Forbes.com. Mar 13, 2014.

5. Blakemore E. “The little-known history of forced sterilization of Native American women.” JSTOR.org. Aug 25, 2016.

6. Bleir G and A Zoledziowski. “Murdered and missing Native American women challenge police and courts.” Publicintegrity.org. Aug 27, 2018.

7. Brockie TN et al. A framework to examine the role of epigenetics in health disparities among Native Americans. Nurs Res Prac. 2013;2013:410395.

8. “Reclaiming power and place: The final report of the national inquiry into missing and murdered Indigenous women and girls.” Vancouver: Privy Office. Jun 3, 2019.

9. Hagan S. “Where U.S. unemployment is still sky-high: Indian reservations.” Bloomberg.com. Apr 5, 2018.

10. Morin B. “Meet 10 Indigenous women who are making the world a better place.” Indian Country Today. Jul 1, 2019.

11. Fact sheet. Discovernavajo.com.

12. Sarche M and P Spicer. Poverty and health disparities for American Indian and Alaska Native children: Current knowledge and future prospects. Ann NY Acad Sci. 2008 Jul 25;1136:126-36.

13. Lewis-Fernández R et al. Culture and psychiatric evaluation: Operationalizing cultural formulation for DSM-5. Psychiatry. 2014 Summer;77(2):130-54.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local Indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating Indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association.

Dr. Neidhardt is a board-certified psychiatrist who lives in Santa Fe and has an integrative, holistic psychiatric practice that also specializes in trauma-focused therapy. He has provided care for Indigenous People in the Southwest United States and in Canada, and has worked with Navajo medicine people to develop training for mental health professionals with his wife, Dr. Mary Hasbah Roessel. Dr. Reinhardt is a life fellow of the APA.

Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

Planned Parenthood will no longer participate in the federal Title X family planning program in response to a Trump administration rule that prohibits physicians from counseling patients about abortion and referring patients for the procedure.

In an Aug. 19 announcement, Alexis McGill Johnson, Planned Parenthood Federation of America president and CEO, said the Title X changes, which amount to “an unethical and dangerous gag rule,” has forced the organization out of Title X after being part of the program for 50 years. Planned Parenthood health centers are the largest Title X provider, serving 40% of patients who receive care through the program.

“We believe that the Trump administration is doing this as an attack on reproductive health care and to keep providers like Planned Parenthood from serving our patients,” Ms. McGill said in a statement. “Health care shouldn’t come down to how much you earn, where you live, or who you are. Congress must act now. It’s time for the U.S. Senate to act to pass a spending bill that will reverse the harmful rule and restore access to birth control, STD testing, and other critical services to people with low incomes.”

In an Aug. 19 statement, Mia Palmieri Heck, director of external affairs for the U.S. Department of Health & Human Services said every current Title X grantee has the choice to accept their grant and comply with the changes, or reject their funding by refusing to comply.

“The new Title X regulations were final at the time the current grant awards were announced,” Ms. Heck said a statement. “Some grantees are now blaming the government for their own actions – having chosen to accept the grant while failing to comply with the regulations that accompany it – and they are abandoning their obligations to serve their patients under the program. HHS is grateful for the many grantees who continue to serve their patients under the Title X program, and we will work to ensure all patients continue to be served.”

The announcement by Planned Parenthood comes about a month after HHS gave family planning clinics more time to comply with the new rule if they are making good faith efforts to comply with the new rules. The changes to the Title X program make health clinics ineligible for funding if they offer, promote, or support abortion as a method of family planning.

So far, more than 20 states and several abortion rights organizations, including Planned Parenthood, have sued over the rules in four separate states. District judges in Oregon, Washington, and California temporarily blocked the rules from taking effect. In a June 20 decision, the 9th U.S. Circuit Court of Appeals ruled that the federal government may go forward with its plan to restrict Title X funding from clinics that provide abortion counseling or referrals. The decision overturned the lower court injunctions.

Clare Coleman, president and CEO for the National Family Planning & Reproductive Health Association, said she expects further withdrawals from the Title X program to follow Planned Parenthood’s departure.

“The administration’s Title X rule is forcing the program’s 90 grantees and nearly 4,000 service sites to make gut-wrenching choices,” Ms. Coleman said in a statement. “They can stay in the program, despite the rule’s harms and compromises to Title X’s quality of care, for the sake of continuing to offer some Title X care for low-income individuals [or] they can leave the program and forego funding in order to avoid the rule’s limits on pregnancy counseling and other essential care, contrary to HHS’s own professional standards.”

HHS has previously said that the Title X changes ensure that grants and contracts awarded under the program fully comply with the statutory program integrity requirements, “thereby fulfilling the purpose of Title X, so that more women and men can receive services that help them consider and achieve both their short-term and long-term family planning needs.” The agency recently posted guidance on its website on myths vs. facts about the changes.

Ms. Johnson meanwhile, said Planned Parenthood clinics will remain open to serve patients, and that the organization will continue to fight the Title X changes in court.



[email protected]




 

A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.

The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.

Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19. Measles cases have been confirmed in 30 states so far this year, according to the CDC.

Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).

“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”

[email protected]

A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.

The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.

Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19. Measles cases have been confirmed in 30 states so far this year, according to the CDC.

Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).

“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”

[email protected]

A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.

The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.

Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19. Measles cases have been confirmed in 30 states so far this year, according to the CDC.

Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).

“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”

[email protected]

The American College of Physicians recently described its methods for developing clinical guidelines and guidance statements, in a paper published in the Annals of Internal Medicine.

The ACP’s Clinical Guidelines Committee (CGC) "aims to disclose all health care–related interests and manage conflicts in a manner that is transparent, proportional, and consistent. Any person involved in the development of an ACP clinical guideline or guidance statement must disclose all financial and intellectual interests related to health care from the previous 3 years,” Amir Qaseem, MD, and Timothy J. Wilt, MD, wrote.

“The goals of our process are to mitigate any actual bias during the development of ACP’s clinical recommendations and to ensure creditability and public trust in our clinical policies by reducing the potential for perceived bias,” noted Robert M. McLean, MD, president of the ACP, in a statement.

This paper’s publication comes on the heels of authors of a Cancer paper having reported that nearly 25% of the American Society of Clinical Oncology’s guideline authors who were not exempt from reporting conflicts of interest failed to disclose receiving industry payments.

The ACP committee’s guiding principle for collection of disclosures of interest and management of conflicts of interests “is to prioritize the interests of the patient over any competing or professional interests via an evidence-based assessment of the benefits, harms, and costs of an intervention,” wrote the authors on behalf of the CGC.

The CGC created a tiered system to classify potential conflicts as low level, moderate level, or high level based on three tenets: transparency (all disclosures are freely accessible so readers can assess them for themselves), proportionality (not all conflicts of interest have equal risk), and consistency (policies should be impartially applied across all variables).

Examples of low-level conflicts of interest (COIs) include high-level COIs that have become inactive and intellectual interests tangentially related to the topic under discussion. Moderate-level COIs are usually intellectual interests clinically relevant to the guideline topic; these interests might prompt an individual to seek professional or financial advantages through association with guideline development.

High-level COIs are active relationships with high-risk entities, defined by the CGC as “an entity that has a direct financial stake in the clinical conclusions of a guideline or guidance statement.”

While the time frame for reporting health-related interests is 3 years, disclosure is an ongoing process when clinical guidelines are in development because interests change over time, the authors said. Prospective guidelines committee members complete disclosure of interest forms before working on CGC projects, and they update these forms before each in-person CGC meeting.

“The CGC’s policy does not mandate disclosure of interests related primarily to personal matters or relationships outside the household,” such as political, religious, or ideological views, they noted.

The CGC maintains a DOI-COI Review and Management Panel to reviews conflicts, and all ACP guidelines include a list of relevant conflicts for committee members.

The authors of this paper disclosed no conflicts of interest.
 

SOURCE: Qaseem A and TJ Wilt. Ann Intern Med. 2019 Aug 20. doi: 10.7326/M18-3279 .

This article was updated 8/22/19.

The American College of Physicians recently described its methods for developing clinical guidelines and guidance statements, in a paper published in the Annals of Internal Medicine.

The ACP’s Clinical Guidelines Committee (CGC) "aims to disclose all health care–related interests and manage conflicts in a manner that is transparent, proportional, and consistent. Any person involved in the development of an ACP clinical guideline or guidance statement must disclose all financial and intellectual interests related to health care from the previous 3 years,” Amir Qaseem, MD, and Timothy J. Wilt, MD, wrote.

“The goals of our process are to mitigate any actual bias during the development of ACP’s clinical recommendations and to ensure creditability and public trust in our clinical policies by reducing the potential for perceived bias,” noted Robert M. McLean, MD, president of the ACP, in a statement.

This paper’s publication comes on the heels of authors of a Cancer paper having reported that nearly 25% of the American Society of Clinical Oncology’s guideline authors who were not exempt from reporting conflicts of interest failed to disclose receiving industry payments.

The ACP committee’s guiding principle for collection of disclosures of interest and management of conflicts of interests “is to prioritize the interests of the patient over any competing or professional interests via an evidence-based assessment of the benefits, harms, and costs of an intervention,” wrote the authors on behalf of the CGC.

The CGC created a tiered system to classify potential conflicts as low level, moderate level, or high level based on three tenets: transparency (all disclosures are freely accessible so readers can assess them for themselves), proportionality (not all conflicts of interest have equal risk), and consistency (policies should be impartially applied across all variables).

Examples of low-level conflicts of interest (COIs) include high-level COIs that have become inactive and intellectual interests tangentially related to the topic under discussion. Moderate-level COIs are usually intellectual interests clinically relevant to the guideline topic; these interests might prompt an individual to seek professional or financial advantages through association with guideline development.

High-level COIs are active relationships with high-risk entities, defined by the CGC as “an entity that has a direct financial stake in the clinical conclusions of a guideline or guidance statement.”

While the time frame for reporting health-related interests is 3 years, disclosure is an ongoing process when clinical guidelines are in development because interests change over time, the authors said. Prospective guidelines committee members complete disclosure of interest forms before working on CGC projects, and they update these forms before each in-person CGC meeting.

“The CGC’s policy does not mandate disclosure of interests related primarily to personal matters or relationships outside the household,” such as political, religious, or ideological views, they noted.

The CGC maintains a DOI-COI Review and Management Panel to reviews conflicts, and all ACP guidelines include a list of relevant conflicts for committee members.

The authors of this paper disclosed no conflicts of interest.
 

SOURCE: Qaseem A and TJ Wilt. Ann Intern Med. 2019 Aug 20. doi: 10.7326/M18-3279 .

This article was updated 8/22/19.

The American College of Physicians recently described its methods for developing clinical guidelines and guidance statements, in a paper published in the Annals of Internal Medicine.

The ACP’s Clinical Guidelines Committee (CGC) "aims to disclose all health care–related interests and manage conflicts in a manner that is transparent, proportional, and consistent. Any person involved in the development of an ACP clinical guideline or guidance statement must disclose all financial and intellectual interests related to health care from the previous 3 years,” Amir Qaseem, MD, and Timothy J. Wilt, MD, wrote.

“The goals of our process are to mitigate any actual bias during the development of ACP’s clinical recommendations and to ensure creditability and public trust in our clinical policies by reducing the potential for perceived bias,” noted Robert M. McLean, MD, president of the ACP, in a statement.

This paper’s publication comes on the heels of authors of a Cancer paper having reported that nearly 25% of the American Society of Clinical Oncology’s guideline authors who were not exempt from reporting conflicts of interest failed to disclose receiving industry payments.

The ACP committee’s guiding principle for collection of disclosures of interest and management of conflicts of interests “is to prioritize the interests of the patient over any competing or professional interests via an evidence-based assessment of the benefits, harms, and costs of an intervention,” wrote the authors on behalf of the CGC.

The CGC created a tiered system to classify potential conflicts as low level, moderate level, or high level based on three tenets: transparency (all disclosures are freely accessible so readers can assess them for themselves), proportionality (not all conflicts of interest have equal risk), and consistency (policies should be impartially applied across all variables).

Examples of low-level conflicts of interest (COIs) include high-level COIs that have become inactive and intellectual interests tangentially related to the topic under discussion. Moderate-level COIs are usually intellectual interests clinically relevant to the guideline topic; these interests might prompt an individual to seek professional or financial advantages through association with guideline development.

High-level COIs are active relationships with high-risk entities, defined by the CGC as “an entity that has a direct financial stake in the clinical conclusions of a guideline or guidance statement.”

While the time frame for reporting health-related interests is 3 years, disclosure is an ongoing process when clinical guidelines are in development because interests change over time, the authors said. Prospective guidelines committee members complete disclosure of interest forms before working on CGC projects, and they update these forms before each in-person CGC meeting.

“The CGC’s policy does not mandate disclosure of interests related primarily to personal matters or relationships outside the household,” such as political, religious, or ideological views, they noted.

The CGC maintains a DOI-COI Review and Management Panel to reviews conflicts, and all ACP guidelines include a list of relevant conflicts for committee members.

The authors of this paper disclosed no conflicts of interest.
 

SOURCE: Qaseem A and TJ Wilt. Ann Intern Med. 2019 Aug 20. doi: 10.7326/M18-3279 .

This article was updated 8/22/19.

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

Lipophilic statin therapy significantly reduced the incidence and mortality of hepatocellular carcinoma in adults with viral hepatitis, based on data from 16,668 patients.

The mortality rates for hepatocellular carcinoma in the United States and Europe have been on the rise for decades, and the risk may persist in severe cases despite the use of hepatitis B virus suppression or hepatitis C virus eradication, wrote Tracey G. Simon, MD, of Harvard Medical School, Boston, and colleagues. Previous studies suggest that statins might reduce HCC risk in viral hepatitis patients, but evidence supporting one type of statin over another for HCC prevention is limited, they said.

In a study published in the Annals of Internal Medicine, the researchers reviewed data from a national registry of hepatitis patients in Sweden to assess the effect of lipophilic or hydrophilic statin use on HCC incidence and mortality.

They found a significant reduction in 10-year HCC risk for lipophilic statin users, compared with nonusers (8.1% vs. 3.3%. However, the difference was not significant for hydrophilic statin users vs. nonusers (8.0% vs. 6.8%). The effect of lipophilic statin use was dose dependent; the largest effect on reduction in HCC risk occurred with 600 or more lipophilic statin cumulative daily doses in users, compared with nonusers (8.4% vs. 2.5%).

The study population included 6,554 lipophilic statin users and 1,780 hydrophilic statin users, matched with 8,334 nonusers. Patient demographics were similar between both types of statin user and nonuser groups.

In addition, 10-year mortality was significantly lower for lipophilic statin users compared with nonusers (15.2% vs. 7.3%) and also for hydrophilic statin users, compared with nonusers (16.0% vs. 11.5%).

In a small number of patients with liver disease (462), liver-specific mortality was significantly reduced in lipophilic statin users, compared with nonusers (adjusted hazard ratio, 0.76 vs. 0.98).

“Of note, our findings were robust across several sensitivity analyses and were similar in all predefined subgroups, including among men and women and persons with and without cirrhosis or antiviral therapy use,” the researchers noted.

The study findings were limited by several factors including the potential confounding from variables such as smoking, hepatitis B viral DNA, hepatitis C virus eradication, stage of fibrosis, and HCC screening, as well as a lack of laboratory data to assess cholesterol levels’ impact on statin use, the researchers said. In addition, the study did not compare lipophilic and hydrophilic statins.

However, the results suggest potential distinct benefits of lipophilic statins to reduce HCC risk and support the need for further research, the researchers concluded.

Dr. Simon had no financial conflicts to disclose, but disclosed support from a North American Training Grant from the American College of Gastroenterology. Several coauthors disclosed relationships with multiple companies including AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and Merck Sharp & Dohme. The study was supported in part by the American College of Gastroenterology, the American Association for the Study of Liver Diseases, the Boston Nutrition Obesity Research Center, the National Institutes of Health, Nyckelfonden, Region Orebro (Sweden) County, and the Karolinska Institutet.
 

SOURCE: Simon TG et al. Ann Intern Med. 2019 Aug 19. doi: 10.7326/M18-2753.

LAKE BUENA VISTA, FLA. – Digital health technology is vastly expanding the real-world data pool for clinical and comparative effectiveness research, according to Jeffrey Curtis, MD.

HASLOO/ThinkStock

The trick is to harness the power of that data to improve patient care and outcomes, and that can be achieved in part through linkage of data sources and through point-of-care access, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

“We want to take care of patients, but probably what you and I also want is to have real-world evidence ... evidence relevant for people [we] take care of on a day-to-day basis – not people in highly selected phase 3 or even phase 4 trials,” he said.

Real-world data, which gained particular cachet through the 21st Century Cures Act permitting the Food and Drug Administration to consider real-world evidence as part of the regulatory process and in post-marketing surveillance, includes information from electronic health records (EHRs), health plan claims, traditional registries, and mobile health and technology, explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Courtesy University of Alabama at Birmingham

“And you and I want it because patients are different, and in medicine we only have about 20% of patients where there is direct evidence about what we should do,” he added. “Give me the trial that describes the 75-year-old African American smoker with diabetes and how well he does on biologic du jour; there’s no trial like that, and yet you and I need to make those kinds of decisions in light of patients’ comorbidities and other features.”

Generating real-world evidence, however, requires new approaches and new tools, he said, explaining that efficiency is key for applying the data in busy practices, as is compatibility with delivering an intervention and with randomization.

Imagine using the EHR at the point of care to look up what happened to “the last 10 patients like this” based on how they were treated by you or your colleagues, he said.

“That would be useful information to have. In fact, the day is not so far in the future where you could, perhaps, randomize within your EHR if you had a clinically important question that really needed an answer and a protocol attached,” he added.
 

Real-world data collection

Pragmatic trials offer one approach to garnering real-world data by addressing a simple question – usually with a hard outcome – using very few inclusion and exclusion criteria, Dr. Curtis said, describing the recently completed VERVE Zoster Vaccine trial.

He and his colleagues randomized 617 patients from 33 sites to look at the safety of the live-virus Zostavax herpes zoster vaccine in rheumatoid arthritis patients over age 50 years on any anti–tumor necrosis factor (anti-TNF) therapy. Half of the patients received saline, the other half received the vaccine, and no cases of varicella zoster occurred in either group.

“So, to the extent that half of 617 people with zero cases was reassuring, we now have some evidence where heretofore there was none,” he said, noting that those results will be presented at the 2019 American College of Rheumatology annual meeting. “But the focus of this talk is not on vaccination, it’s really on how we do real-world effectiveness or safety studies in a way that doesn’t slow us way down and doesn’t require some big research operation.”

One way is through efficient recruitment, and depending on how complicated the study is, qualified patients may be easily identifiable through the EHR. In fact, numerous tools are available to codify and search both structured and unstructured data, Dr. Curtis said, noting that he and his colleagues used the web-based i2b2 Query Tool for the VERVE study.

The study sites that did the best with recruiting had the ability to search their own EHRs for patients who met the inclusion criteria, and those patients were then invited to participate. A short video was created to educate those who were interested, and a “knowledge review” quiz was administered afterward to ensure informed consent, which was provided via digital signature.

Health plan and other “big data” can also be very useful for answering certain questions. One example is how soon biologics should be stopped before elective orthopedic surgery? Dr. Curtis and colleagues looked at this using claims data for nearly 4,300 patients undergoing elective hip or knee arthroplasty and found no evidence that administering infliximab within 4 weeks of surgery increased serious infection risk within 30 days or prosthetic joint infection within 1 year.

“Where else are you going to go run a prospective study of 4,300 elective hips and knees,” he said, stressing that it wouldn’t be easy.

Other sources that can help generate real-world effectiveness data include traditional or single-center registries and EHR-based registries.

“The EHR registries are, I think, the newest that many are part of in our field,” he said, noting that “a number of groups are aggregating that,” including the ACR RISE registry and some physician groups, for example.

“What we’re really after is to have a clinically integrated network and a learning health care environment,” he explained, adding that the goal is to develop care pathways.

The approach represents a shift from evidence-based practice to practice-based evidence, he noted.

“When you and I practice, we’re generating that evidence and now we just need to harness that data to get smarter to take care of patients,” he said, adding that the lack of randomization for much of these data isn’t necessarily a problem.

“Do you have to randomize? I would argue that you don’t necessarily have to randomize if the source of variability in how we treat patients is very related to patients’ characteristics,” he said.

If the evidence for a specific approach is weak, or a decision is based on physician preference, physician practice, or insurance company considerations instead of patient characteristics, randomization may not be necessary, he explained.

In fact, insurance company requirements often create “natural experiments” that can be used to help identify better practices. For example, if one only covers adalimumab for first-line TNF inhibition, and another has a “different fail-first policy and that’s not first line and everybody gets some other TNF inhibitor, then I can probably compare those quite reasonably,” he said.

“That’s a great setting where you might not need randomization.”

Of note, “having more data sometimes trumps smarter algorithms,” but that means finding and linking more data that “exist in the wild,” Dr. Curtis said.

Linking data sources

When he and his colleagues wanted to assess the cost of not achieving RA remission, no single data source provided all of the information they needed. They used both CORRONA registry data and health claims data to look at various outcome measures across disease activity categories and with adjustment for comorbidity clusters. They previously reported on the feasibility and validity of the approach.

“We’re currently doing another project where one of the local Blue Cross plans said ‘I’m interested to support you to see how efficient you are; we will donate or loan you our claims data [and] let you link it to your practice so you can actually tell us ... cost conditional on [a patient’s] disease activity,’ ” he said.

Another example involves a recent study looking at biomarker-based cardiovascular disease risk prediction in RA using data from nearly 31,000 Medicare patients linked with multibiomarker disease activity (MBDA) test results, with which they “basically built and validated a risk prediction model,” he said.

The point is that such data linkage provided tools for use at the point of care that can predict CVD risk using “some simple things that you and I have in our EHR,” he said. “But you couldn’t do this if you had to assemble a prospective cohort of tens of thousands of arthritis patients and then wait years for follow-up.”

Patient-reported outcomes collected at the point of care and by patients at home between visits, such as digital data collected via wearable technology, can provide additional information to help improve patient care and management.

“My interest is not to think about [these data sources] in isolation, but really to think about how we bring these together,” he said. “I’m interested in maximizing value for both patients and clinicians, and not having to pick only one of these data sources, but really to harness several of them if that’s what we need to take better care of patients and to answer important questions.”

Doing so is increasingly important given the workforce shortage in rheumatology, he noted.

“The point is that we’re going to need to be a whole lot more efficient as a field because there are going to be fewer of us even at a time when more of us are needed,” he said.

It’s a topic in which the ACR has shown a lot of interest, he said, noting that he cochaired a preconference course on mobile health technologies at the 2018 ACR annual meeting and is involved with a similar course on “big data” ahead of the 2019 meeting.

The thought of making use of the various digital health and “big data” sources can be overwhelming, but the key is to start with the question that needs an answer or the problem that needs to be solved.

“Don’t start with the data,” he explained. “Start with [asking] ... ‘What am I trying to do?’ ”

Dr. Curtis reported funding from the National Institute on Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

LAKE BUENA VISTA, FLA. – Digital health technology is vastly expanding the real-world data pool for clinical and comparative effectiveness research, according to Jeffrey Curtis, MD.

HASLOO/ThinkStock

The trick is to harness the power of that data to improve patient care and outcomes, and that can be achieved in part through linkage of data sources and through point-of-care access, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

“We want to take care of patients, but probably what you and I also want is to have real-world evidence ... evidence relevant for people [we] take care of on a day-to-day basis – not people in highly selected phase 3 or even phase 4 trials,” he said.

Real-world data, which gained particular cachet through the 21st Century Cures Act permitting the Food and Drug Administration to consider real-world evidence as part of the regulatory process and in post-marketing surveillance, includes information from electronic health records (EHRs), health plan claims, traditional registries, and mobile health and technology, explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Courtesy University of Alabama at Birmingham

“And you and I want it because patients are different, and in medicine we only have about 20% of patients where there is direct evidence about what we should do,” he added. “Give me the trial that describes the 75-year-old African American smoker with diabetes and how well he does on biologic du jour; there’s no trial like that, and yet you and I need to make those kinds of decisions in light of patients’ comorbidities and other features.”

Generating real-world evidence, however, requires new approaches and new tools, he said, explaining that efficiency is key for applying the data in busy practices, as is compatibility with delivering an intervention and with randomization.

Imagine using the EHR at the point of care to look up what happened to “the last 10 patients like this” based on how they were treated by you or your colleagues, he said.

“That would be useful information to have. In fact, the day is not so far in the future where you could, perhaps, randomize within your EHR if you had a clinically important question that really needed an answer and a protocol attached,” he added.
 

Real-world data collection

Pragmatic trials offer one approach to garnering real-world data by addressing a simple question – usually with a hard outcome – using very few inclusion and exclusion criteria, Dr. Curtis said, describing the recently completed VERVE Zoster Vaccine trial.

He and his colleagues randomized 617 patients from 33 sites to look at the safety of the live-virus Zostavax herpes zoster vaccine in rheumatoid arthritis patients over age 50 years on any anti–tumor necrosis factor (anti-TNF) therapy. Half of the patients received saline, the other half received the vaccine, and no cases of varicella zoster occurred in either group.

“So, to the extent that half of 617 people with zero cases was reassuring, we now have some evidence where heretofore there was none,” he said, noting that those results will be presented at the 2019 American College of Rheumatology annual meeting. “But the focus of this talk is not on vaccination, it’s really on how we do real-world effectiveness or safety studies in a way that doesn’t slow us way down and doesn’t require some big research operation.”

One way is through efficient recruitment, and depending on how complicated the study is, qualified patients may be easily identifiable through the EHR. In fact, numerous tools are available to codify and search both structured and unstructured data, Dr. Curtis said, noting that he and his colleagues used the web-based i2b2 Query Tool for the VERVE study.

The study sites that did the best with recruiting had the ability to search their own EHRs for patients who met the inclusion criteria, and those patients were then invited to participate. A short video was created to educate those who were interested, and a “knowledge review” quiz was administered afterward to ensure informed consent, which was provided via digital signature.

Health plan and other “big data” can also be very useful for answering certain questions. One example is how soon biologics should be stopped before elective orthopedic surgery? Dr. Curtis and colleagues looked at this using claims data for nearly 4,300 patients undergoing elective hip or knee arthroplasty and found no evidence that administering infliximab within 4 weeks of surgery increased serious infection risk within 30 days or prosthetic joint infection within 1 year.

“Where else are you going to go run a prospective study of 4,300 elective hips and knees,” he said, stressing that it wouldn’t be easy.

Other sources that can help generate real-world effectiveness data include traditional or single-center registries and EHR-based registries.

“The EHR registries are, I think, the newest that many are part of in our field,” he said, noting that “a number of groups are aggregating that,” including the ACR RISE registry and some physician groups, for example.

“What we’re really after is to have a clinically integrated network and a learning health care environment,” he explained, adding that the goal is to develop care pathways.

The approach represents a shift from evidence-based practice to practice-based evidence, he noted.

“When you and I practice, we’re generating that evidence and now we just need to harness that data to get smarter to take care of patients,” he said, adding that the lack of randomization for much of these data isn’t necessarily a problem.

“Do you have to randomize? I would argue that you don’t necessarily have to randomize if the source of variability in how we treat patients is very related to patients’ characteristics,” he said.

If the evidence for a specific approach is weak, or a decision is based on physician preference, physician practice, or insurance company considerations instead of patient characteristics, randomization may not be necessary, he explained.

In fact, insurance company requirements often create “natural experiments” that can be used to help identify better practices. For example, if one only covers adalimumab for first-line TNF inhibition, and another has a “different fail-first policy and that’s not first line and everybody gets some other TNF inhibitor, then I can probably compare those quite reasonably,” he said.

“That’s a great setting where you might not need randomization.”

Of note, “having more data sometimes trumps smarter algorithms,” but that means finding and linking more data that “exist in the wild,” Dr. Curtis said.

Linking data sources

When he and his colleagues wanted to assess the cost of not achieving RA remission, no single data source provided all of the information they needed. They used both CORRONA registry data and health claims data to look at various outcome measures across disease activity categories and with adjustment for comorbidity clusters. They previously reported on the feasibility and validity of the approach.

“We’re currently doing another project where one of the local Blue Cross plans said ‘I’m interested to support you to see how efficient you are; we will donate or loan you our claims data [and] let you link it to your practice so you can actually tell us ... cost conditional on [a patient’s] disease activity,’ ” he said.

Another example involves a recent study looking at biomarker-based cardiovascular disease risk prediction in RA using data from nearly 31,000 Medicare patients linked with multibiomarker disease activity (MBDA) test results, with which they “basically built and validated a risk prediction model,” he said.

The point is that such data linkage provided tools for use at the point of care that can predict CVD risk using “some simple things that you and I have in our EHR,” he said. “But you couldn’t do this if you had to assemble a prospective cohort of tens of thousands of arthritis patients and then wait years for follow-up.”

Patient-reported outcomes collected at the point of care and by patients at home between visits, such as digital data collected via wearable technology, can provide additional information to help improve patient care and management.

“My interest is not to think about [these data sources] in isolation, but really to think about how we bring these together,” he said. “I’m interested in maximizing value for both patients and clinicians, and not having to pick only one of these data sources, but really to harness several of them if that’s what we need to take better care of patients and to answer important questions.”

Doing so is increasingly important given the workforce shortage in rheumatology, he noted.

“The point is that we’re going to need to be a whole lot more efficient as a field because there are going to be fewer of us even at a time when more of us are needed,” he said.

It’s a topic in which the ACR has shown a lot of interest, he said, noting that he cochaired a preconference course on mobile health technologies at the 2018 ACR annual meeting and is involved with a similar course on “big data” ahead of the 2019 meeting.

The thought of making use of the various digital health and “big data” sources can be overwhelming, but the key is to start with the question that needs an answer or the problem that needs to be solved.

“Don’t start with the data,” he explained. “Start with [asking] ... ‘What am I trying to do?’ ”

Dr. Curtis reported funding from the National Institute on Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

LAKE BUENA VISTA, FLA. – Digital health technology is vastly expanding the real-world data pool for clinical and comparative effectiveness research, according to Jeffrey Curtis, MD.

HASLOO/ThinkStock

The trick is to harness the power of that data to improve patient care and outcomes, and that can be achieved in part through linkage of data sources and through point-of-care access, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.

“We want to take care of patients, but probably what you and I also want is to have real-world evidence ... evidence relevant for people [we] take care of on a day-to-day basis – not people in highly selected phase 3 or even phase 4 trials,” he said.

Real-world data, which gained particular cachet through the 21st Century Cures Act permitting the Food and Drug Administration to consider real-world evidence as part of the regulatory process and in post-marketing surveillance, includes information from electronic health records (EHRs), health plan claims, traditional registries, and mobile health and technology, explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.

Courtesy University of Alabama at Birmingham

“And you and I want it because patients are different, and in medicine we only have about 20% of patients where there is direct evidence about what we should do,” he added. “Give me the trial that describes the 75-year-old African American smoker with diabetes and how well he does on biologic du jour; there’s no trial like that, and yet you and I need to make those kinds of decisions in light of patients’ comorbidities and other features.”

Generating real-world evidence, however, requires new approaches and new tools, he said, explaining that efficiency is key for applying the data in busy practices, as is compatibility with delivering an intervention and with randomization.

Imagine using the EHR at the point of care to look up what happened to “the last 10 patients like this” based on how they were treated by you or your colleagues, he said.

“That would be useful information to have. In fact, the day is not so far in the future where you could, perhaps, randomize within your EHR if you had a clinically important question that really needed an answer and a protocol attached,” he added.
 

Real-world data collection

Pragmatic trials offer one approach to garnering real-world data by addressing a simple question – usually with a hard outcome – using very few inclusion and exclusion criteria, Dr. Curtis said, describing the recently completed VERVE Zoster Vaccine trial.

He and his colleagues randomized 617 patients from 33 sites to look at the safety of the live-virus Zostavax herpes zoster vaccine in rheumatoid arthritis patients over age 50 years on any anti–tumor necrosis factor (anti-TNF) therapy. Half of the patients received saline, the other half received the vaccine, and no cases of varicella zoster occurred in either group.

“So, to the extent that half of 617 people with zero cases was reassuring, we now have some evidence where heretofore there was none,” he said, noting that those results will be presented at the 2019 American College of Rheumatology annual meeting. “But the focus of this talk is not on vaccination, it’s really on how we do real-world effectiveness or safety studies in a way that doesn’t slow us way down and doesn’t require some big research operation.”

One way is through efficient recruitment, and depending on how complicated the study is, qualified patients may be easily identifiable through the EHR. In fact, numerous tools are available to codify and search both structured and unstructured data, Dr. Curtis said, noting that he and his colleagues used the web-based i2b2 Query Tool for the VERVE study.

The study sites that did the best with recruiting had the ability to search their own EHRs for patients who met the inclusion criteria, and those patients were then invited to participate. A short video was created to educate those who were interested, and a “knowledge review” quiz was administered afterward to ensure informed consent, which was provided via digital signature.

Health plan and other “big data” can also be very useful for answering certain questions. One example is how soon biologics should be stopped before elective orthopedic surgery? Dr. Curtis and colleagues looked at this using claims data for nearly 4,300 patients undergoing elective hip or knee arthroplasty and found no evidence that administering infliximab within 4 weeks of surgery increased serious infection risk within 30 days or prosthetic joint infection within 1 year.

“Where else are you going to go run a prospective study of 4,300 elective hips and knees,” he said, stressing that it wouldn’t be easy.

Other sources that can help generate real-world effectiveness data include traditional or single-center registries and EHR-based registries.

“The EHR registries are, I think, the newest that many are part of in our field,” he said, noting that “a number of groups are aggregating that,” including the ACR RISE registry and some physician groups, for example.

“What we’re really after is to have a clinically integrated network and a learning health care environment,” he explained, adding that the goal is to develop care pathways.

The approach represents a shift from evidence-based practice to practice-based evidence, he noted.

“When you and I practice, we’re generating that evidence and now we just need to harness that data to get smarter to take care of patients,” he said, adding that the lack of randomization for much of these data isn’t necessarily a problem.

“Do you have to randomize? I would argue that you don’t necessarily have to randomize if the source of variability in how we treat patients is very related to patients’ characteristics,” he said.

If the evidence for a specific approach is weak, or a decision is based on physician preference, physician practice, or insurance company considerations instead of patient characteristics, randomization may not be necessary, he explained.

In fact, insurance company requirements often create “natural experiments” that can be used to help identify better practices. For example, if one only covers adalimumab for first-line TNF inhibition, and another has a “different fail-first policy and that’s not first line and everybody gets some other TNF inhibitor, then I can probably compare those quite reasonably,” he said.

“That’s a great setting where you might not need randomization.”

Of note, “having more data sometimes trumps smarter algorithms,” but that means finding and linking more data that “exist in the wild,” Dr. Curtis said.

Linking data sources

When he and his colleagues wanted to assess the cost of not achieving RA remission, no single data source provided all of the information they needed. They used both CORRONA registry data and health claims data to look at various outcome measures across disease activity categories and with adjustment for comorbidity clusters. They previously reported on the feasibility and validity of the approach.

“We’re currently doing another project where one of the local Blue Cross plans said ‘I’m interested to support you to see how efficient you are; we will donate or loan you our claims data [and] let you link it to your practice so you can actually tell us ... cost conditional on [a patient’s] disease activity,’ ” he said.

Another example involves a recent study looking at biomarker-based cardiovascular disease risk prediction in RA using data from nearly 31,000 Medicare patients linked with multibiomarker disease activity (MBDA) test results, with which they “basically built and validated a risk prediction model,” he said.

The point is that such data linkage provided tools for use at the point of care that can predict CVD risk using “some simple things that you and I have in our EHR,” he said. “But you couldn’t do this if you had to assemble a prospective cohort of tens of thousands of arthritis patients and then wait years for follow-up.”

Patient-reported outcomes collected at the point of care and by patients at home between visits, such as digital data collected via wearable technology, can provide additional information to help improve patient care and management.

“My interest is not to think about [these data sources] in isolation, but really to think about how we bring these together,” he said. “I’m interested in maximizing value for both patients and clinicians, and not having to pick only one of these data sources, but really to harness several of them if that’s what we need to take better care of patients and to answer important questions.”

Doing so is increasingly important given the workforce shortage in rheumatology, he noted.

“The point is that we’re going to need to be a whole lot more efficient as a field because there are going to be fewer of us even at a time when more of us are needed,” he said.

It’s a topic in which the ACR has shown a lot of interest, he said, noting that he cochaired a preconference course on mobile health technologies at the 2018 ACR annual meeting and is involved with a similar course on “big data” ahead of the 2019 meeting.

The thought of making use of the various digital health and “big data” sources can be overwhelming, but the key is to start with the question that needs an answer or the problem that needs to be solved.

“Don’t start with the data,” he explained. “Start with [asking] ... ‘What am I trying to do?’ ”

Dr. Curtis reported funding from the National Institute on Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.

[email protected]

In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.

By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.

“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.

Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.

The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.

Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.

OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.

By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.

The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.

After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).

The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.

SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.

In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.

By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.

“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.

Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.

The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.

Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.

OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.

By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.

The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.

After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).

The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.

SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.

In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.

By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.

“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.

Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.

The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.

Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.

OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.

By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.

The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.

After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).

The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.

SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.